41P - Association of p53-autoantibodies with TP53 somatic mutational profile detected by next generation sequencing in advanced high-grade ovarian cancer...

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Non-Small-Cell Lung Cancer, Early Stage
Cancer in Special Situations
Lung and other Thoracic Tumours
Presenter Marica Garziera
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors M. Garziera1, E. Cecchin1, J. Polesel2, R. Roncato1, S. Gagno1, E. De Mattia1, R. Sorio3, S. Scalone3, E. Poletto4, G. Toffoli1
  • 1Experimental And Clinical Pharmacology Unit, Centro di Riferimento Oncologico, CRO Aviano National Cancer Institute, IRCCS, 33081 - Aviano/IT
  • 2Unit Of Cancer Epidemiology, Centro di Riferimento Oncologico, CRO Aviano National Cancer Institute, IRCCS, 33081 - Aviano/IT
  • 3Medical Oncology C, Centro di Riferimento Oncologico, CRO Aviano National Cancer Institute, IRCCS, 33081 - Aviano/IT
  • 4Oncologic Department, University of Udine, 33100 - Udine/IT

Abstract

Background

TP53 somatic mutations have been suspected to induce an autoantibody immune response against p53. The aim of this study was to determine if a specific TP53 tumor mutational status, is associated with the presence of circulating p53-autoantibodies (p53-AAbs) in patients with advanced high grade ovarian cancer (HGOC).

Methods

A retrospective study was carried out in 117 patients with stage III-IV and high grade (G2-G3) tumors, who were enrolled at CRO Institute and provided adequate tissue sample. All patients underwent surgical debulking and received platinum-based regimen. Matched tumor and blood DNA samples were analyzed for TP53 genetic mutations using a MiSeq platform. Commercially available ELISA kit was used to detect p53-AAbs in plasma or serum.

Results

Median age of the patients was 58 years (range 31-82). Median follow-up time was 40 months (IQ range 20-67). TP53 somatic mutations were found in 74,4% (87/117) of HGOC patients and 26,5% (31/117) were positive for p53-AAbs. Among mutated patients, 28.7% (25/87) was tested positive for presence of p53-AAbs and 71.3% (62/87) was p53-AAbs negative (Fisher’s exact test; p=0.473). In p53-AAbs positive patients with at least a TP53 mutation in matched tumor (81%, 25/31), missense mutations were strongly associated with the presence of p53-AAbs while insertion/deletion, splice/intronic and nonsense variants were associated with p53-AAbs negative patients (p

Conclusions

This study for the first time compared data from the genetic TP53 tumor status through an NGS approach with the presence of circulating p53-AAbs. In most of HGOC, the presence of p53-AAbs was associated with tumors harboring TP53 missense mutations that share GOF effects. These new findings suggest that a specific mutational status in the HGOC tumor is associated with presence of p53-AAbs, but not completely explain the amount of p53-AAbs appearance. Both markers should be further explored and evaluated for impact on clinical outcome.

Clinical trial identification

Legal entity responsible for the study

CRO-National Cancer Institute

Funding

None

Disclosure

All authors have declared no conflicts of interest.